Histone H3 tail positioning and acetylation by the c-Myb but not the v-Myb DNA-binding SANT domain

Xianming Mo, Elisabeth Kowenz-Leutz, Yves Laumonnier, Hong Xu, Achim Leutz*

*Korrespondierende/r Autor/-in für diese Arbeit
53 Zitate (Scopus)

Abstract

The c-Myb transcription factor coordinates proliferation and differentiation of hematopoietic precursor cells. Myb has three consecutive N-terminal SANT-type repeat domains (R1, R2, R3), two of which (R2, R3) form the DNA-binding domain (DBD). Three amino acid substitutions in R2 alter the way Myb regulates genes and determine the leukemogenicity of the retrovirally transduced v-Myb oncogene. The molecular mechanism of how these mutations unleash the leukemogenic potential of Myb is unknown. Here we demonstrate that the c-Myb-DBD binds to the N-terminal histone tails of H3 and H3.3. C-Myb binding facilitates histone tail acetylation, which is mandatory during activation of prevalent differentiation genes in conjunction with CCAAT enhancer-binding proteins (C/EBP). Leukemogenic mutations in v-Myb eliminate the interaction with H3 and acetylation of H3 tails and abolish activation of endogenous differentiation genes. In primary v-myb-transformed myeloblasts, pharmacologic enhancement of H3 acetylation restored activation of differentiation genes and induced cell differentiation. Our data link a novel chromatin function of c-Myb with lineage-specific expression of differentiation genes and relate the loss of this function with the leukemic conversion of Myb.

OriginalspracheEnglisch
ZeitschriftGenes and Development
Jahrgang19
Ausgabenummer20
Seiten (von - bis)2447-2457
Seitenumfang11
ISSN0890-9369
DOIs
PublikationsstatusVeröffentlicht - 15.10.2005

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

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